Coccidiosis, caused by protozoans of the genera Eimeria and Isospora, may be present in any domesticated animal species but is ubiquitous in the poultry industry with serious consequences. The life cycle involves both asexual and sexual intracellular parasitic stages characterized by a rapid development and multiplication of infective stages with consequent destruction of, primarily, the intestinal lining of the host.
Coccidia species are cosmopolitan and widespread in the animal kingdom, although most of them are limited to a narrow range of host species and organ systems. Some coccidia, e.g. Toxoplasma, may pass from one host species to another changing their target organs from host to host. The life cycle of Coccidia includes cysts, sporozoites, schizonts, merozoites, and gametocytes. Eimeria and Toxoplasma are economically and medically important coccidia.
Eimeria infect many vertebrates, including fish, poultry, farm animals, dogs and cats. The parasite first invades the epithelial lining of the digestive tract and may cause diarrhea, sloughing, and ulceration of the intestinal lining, and hemorrhage, metabolic imbalance, and anemia and bacteremia. Depending on severity and duration, the consequences may range from growth retardation to death.
Eradication of Eimeria species with presently available drugs would be impractical because of toxicological and economic considerations. Accordingly, anticoccidials are currently used in animal husbandry as coccidiostats. Mixed with feeds, the cocciodiostats serve to minimize the intensity of infection or to reduce clinical symptoms to a nonfatal course. In this way, time is gained for the host to build up immune defenses. Eimeria species develop drug resistance quite rapidly so that development of new anticoccidials is economically vital for animal farming. Anticoccidial agents are added routinely as feed components throughout the life of broiler chickens. A partial list of additives includes amprolium, ethopabate, robenidine, arprinocid, monensin, lasalocid, chlortetracycline, and the sulfa compounds. Historically, the appearance of resistance by the coccidia to anticoccidial agents has been rapid and frustrating. This resistance has not yet been observed to any notable degree with the ionophores even after more than a decade of extensive use. A program of rotation, where anticoccidials with differing modes of action are used in succession minimizes the impact of resistance.
One group of coccidiostats (i.e., anticoccidial agents) are ionophore coccidiostats. The most widely used additives are compounds capable of transporting cations into or through a lipophilic environment, which compounds are termed "ionophores". Ionophores are compounds such as polyether antibiotics as well as synthetic crown ethers, cryptates, cyclodepsipeptides and macrotetralieds antibiotics. The polyethers are distinguished from these other ionophores, however, in being acids which yield neutral salt complexes, whereas valinomycin and many of the other naturally occurring ionophores are neutral cyclic structures which yield positively charged cation complexes. The name polyether has become the term of choice to characterize these antibiotics as a result of multiplicity of cyclic ethers found in all members of this unique group of microbial products. Representative of the ionophore antibiotics are compounds such as monensin, lasalocid and salinomycin.
Known polyether antibiotics are isolated from the Streptomyces genus of microorganisms. More than thirty polyether antibiotics have been reported. The polyethers exhibit good in vitro activity against gram-positive and mycobacteria but do not inhibit gram-negative microorganisms. Some of the compounds have been reported active against phytopathogenic bacteria and fungi. Due to the high parenteral toxicity of the polyethers, they have found no use as clinical antibacterial agents, but are playing an increasing role in veterinary medicine as coccidiostats in poultry and growth promotants in ruminants such as cattle and sheep.
Improvements in the means of controlling coccidiosis in animals, especially poultry, remains a need in animal husbandry and food industries.